Squamous cell carcinoma is the most common malignant neoplasm of the head and neck. It constitutes at least 75% of head and neck cancer in which patients show a high incidence of immunologic deficiencies and inflammatory symptoms. Despite improvements in the treatment modalities over the past 40 years, the 5-year survival rate of approximately 30% has not changed in the same period.
Oral squamous cell carcinoma has been linked to excessive cigarette smoking and alcohol abuse, both individually and in combination. Other factors associated with oral cancer include poor dental hygiene and malfitting dentures or broken teeth that cause chronic mucosal irritation. Occupational hazards include chronic dust exposure among woodworkers, which has been associated with cancer of the nasopharynx, and exposure to nickel compounds, which increases the risk of paranasal sinus cancers.
Epstein-Barr virus (EBV), the etiologic agent of infectious mononucleosis, has been associated with nasopharyngeal carcinoma. Other viruses have also been implicated, including oral herpes simplex virus type 1 and endogenous oncornaviruses.
Radiation exposure, as well as dietary deficiencies, may also predispose persons to head and neck cancers.
About 90% of oral cancers are detected in only a few high-risk sites; the floor of the mouth, the ventrolateral aspect of the tongue, and the soft palate complex. Buccal and labial vestibular carcinoma should be considered in people who use smokeless tobacco.
Cancer of the head and neck occurs in four major anatomic sites: the oral cavity, pharynx, larynx, and nasal and paranasal sinuses. These sites are subdivided into various component regions. The most common sites of disease are the oral cavity and the oropharynx, which account for slightly less than 50% of cases, followed by the larynx, which accounts for about 30% of cases.
Early, asymptomatic oral cancer appears most often as a red (erythroplastic) lesion. Squamous cell carcinoma, not diagnosed in its earliest stages appears later as a deep ulcer with smooth, indurated, rolled margins, fixed to deeper tissues. Biopsy is necessary to diagnose carcinoma.
Squamous cell carcinomas are often diagnosed early because such cancers lead to local symptoms such as pain, hoarseness, and difficulty in swallowing. In many cases, however, diagnosis is delayed because local symptoms or pain from nerve involvement does not occur until a large primary tumor develops. In such cases, regional nodal metastases may be the initial manifestation. Distant metastases rarely occur without locally advanced primary disease or nodal involvement.
Head and neck cancer may be a panmucosal disease of the upper aerodigestive tract; additional silent synchronous primary lesions occur frequently. Patients with such a clinical picture are predisposed to additional primary head and neck cancers at a later date (the incidence is approximately three to five percent a year).
Although there are few tumor markers for head and neck cancer, the serum ferritin level is reported to accurately reflect the stage and course of disease. (Ferritin is a major iron-storage protein of human tissues and is found in small quantities in the serum.) However, an elevated serum ferritin level is not specific for head and neck cancer; its level is also elevated in other cancers and in nonmalignant conditions.
Levels of antibodies to EBV in both established and occult nasopharyngeal carcinoma may be used as a diagnostic tool. Measurements of IgA antibodies to viral capsid antigen (anti-VCA) and of IgG antibodies to early antigen (anti-EA) are the most specific tests, particularly for the undifferentiated types of Nasopharyngeal Carcinoma (NPC).
Cancers of the head and neck are staged according to the TNM system of the American Joint Committee on Cancer. The classification of the primary tumor (T) varies depending on its site, size, and extent of invasion of and attachment to the surrounding tissues; only tumors of the oral cavity and oropharynx are classified using the same criteria. When the lesion cannot be measured accurately, the number of sites involved is used to determine the T stage. Cervical lymph nodes (N) are classified by the size, number, and distribution (homolateral or bilateral) of affected nodes. Disease is also classified by the presence or absence of distant metastases (M). The overall stage of the disease is determined from the TNM stage: stage I and stage II diseases, which are considered limited diseases, are accurately assessed by clinical evaluation; stage III, or locally advanced, disease mainly includes larger primary tumors with or without regional nodal spread (T.sub.3 N.sub.0, T.sub.1-3 N.sub.1); and stage IV disease consists of either massive, extensively invasive primary lesions with variable patterns of nodal involvement (T.sub.1-4 N.sub.2-3, T.sub.4 N.sub.0-1, or locally advanced disease) or any other TN combination with distant metastases (M.sub.1, or metastatic disease).
Although surgery and radiotherapy remain the mainstays of treatment, chemotherapy is playing an increasingly important role in the management of this disease. Chemotherapy is used for palliation of metastatic or recurrent disease or as initial treatment, in combination with surgery and radiotherapy, for locally advanced disease.
Because squamous cell carcinoma of the head and neck is a heterogeneous disease that can arise in multiple sites, the response rates to surgery, irradiation, and chemotherapy vary with the primary site of disease. Thus, prognosis is related not only to stage and histopathologic features but also to site and, for patients who are undergoing chemotherapy, to prior treatment.
The strategy for treatment is determined by the stage of disease. For early disease, either surgery or radiotherapy can be employed because they give similar survival results. The choice depends on the expected morbidity from treatment (e.g., loss of speech or functional disfigurement from surgery or severe dryness of the mouth or altered taste from radiotherapy) as well as the urgency of treatment. With more locally advanced disease, surgery and radiotherapy are combined because this approach produces improved control of local disease. Radiotherapy may be administered either preoperatively or postoperatively. Prophylactic radiotherapy is often administered for draining lymph node sites, which are at high risk for microscopic involvement. Chemotherapy has been incorporated into the initial treatment plan for patients with locally advanced disease because five-year disease-free survival is generally low for such patients (10 to 30%) when conventional surgery, radiotherapy, or both are used.
There has been increasing concern that methods of treatment such as surgery, radiotherapy and chemotherapy may adversely affect the patient's natural immunity which probably increases the chances of growth of residual or metastatic tumor cells. This has directed attention not only to early detection and better treatment but also to more research on the possible an etiology of the disease.
Research in the area of allergic reactions of the lung has provided evidence that arachidonic acid derivatives formed by the action of lipoxygenases are related to various disease states. Some of these arachidonic acid metabolites have been classified as members of a family of eicosatetraenoic acids termed leukotrienes. Three of these substances are currently thought to be major components of what has been previously called slow reacting substance of anaphylaxis (SRS-A) and have been designated leukotrienes C.sub.4, D.sub.4, and E.sub.4 (LTC.sub.4, LTD.sub.4, and LTE.sub.4, respectively).
Another arachidonic acid metabolite, leukotriene B.sub.4 (LTB.sub.4), is a proinflammatory lipid which has been implicated in the pathogenesis of psoriasis, arthritis, chronic lung diseases, acute respiratory distress syndrome, shock, asthma, inflammatory bowel diseases, and other inflammatory states characterized by the infiltration and activation of polymorphonuclear leukocytes and other proinflammatory cells. Thus activated, the polymorphonuclear leukocytes liberate tissue-degrading enzymes and reactive chemicals causing the inflammation. Antagonism of LTB.sub.4 should therefore provide a novel therapeutic approach to treatment of these and other LTB.sub.4 mediated conditions.
Because of the debilitating effects of oral squamous cell carcinoma there continues to exist a need for effective treatments.